Identification of Maturity-Onset Diabetes of the Young Caused by Mutation in Whole-Exome Sequencing in Northern China.

Diabetes mellitus is a highly heterogeneous disorder encompassing different types with particular clinical manifestations, while maturity-onset diabetes of the young (MODY) is an early-onset monogenenic diabetes. Most genetic predisposition of MODY has been identified in European and American populations. A large number of Chinese individuals are misdiagnosed due to defects of unknown genes. In this study, we analyzed the genetic and clinical characteristics of the Northern China. A total of 200 diabetic patients, including 10 suspected MODY subjects, were enrolled, and the mutational analysis of monogenic genes was performed by whole-exome sequencing and confirmed by familial information and Sanger sequencing. We found that clinical features and genetic characteristics have varied widely between MODY and other diabetic subjects in Northern China. , a key molecule in the proliferation of pancreatic β-cells, has a rare mutation rs535471991, which leads to instability within the phosphorylated domain that impairs its function. Our findings indicate that may play a critical role in MODY, which could reduce the misdiagnose rate and provide promising therapy for MODY patients.